title: Control of pathogen growth and biofilm formation using a urinary catheter that releases antimicrobial nitrogen oxides.
abstract: Antibacterial nitrogen oxides including nitric oxide are formed from nitrite under acidic conditions. In a continuous-flow model of the urinary bladder we used the retention cuff of an all-silicone Foley catheter as a depot for export of nitrogen oxides. The cuff was filled with sodium nitrite (50mM) and an acidic buffer solution (pH 3.6) and the growth of nine common uropathogens in the surrounding artificial urine was measured along with biofilm formation on the catheter surface. In experiments with control catheters (NaCl) bacteria grew readily and biofilm developed within hours in five of nine strains. In contrast, with test catheters bacterial counts were markedly reduced and biofilm formation by Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter cloace was prevented, whereas Escherichia coli and Staphylococcus aureus were unaffected. We conclude that antibacterial nitrogen oxides generated in the retention cuff of a urinary catheter diffuse into urine and prevent the growth of urinary pathogens and biofilm formation. Although promising, future studies will reveal if this novel approach can be clinically useful for the prevention of catheter-associated urinary tract infections.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kishikawa
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Anette
authors.initials: A
authors.lastname: Ebberyd
authors.affiliation: Department of Microbiology, Tumor Biology, and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Ute
authors.initials: U
authors.lastname: Römling
authors.affiliation: Department of Microbiology, Tumor Biology, and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden; Division of Clinical Microbiology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Brauner
authors.affiliation: Department of Microbiology, Tumor Biology, and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden; Division of Clinical Microbiology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Petra
authors.initials: P
authors.lastname: Lüthje
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. Electronic address: eddie.weitzberg@ki.se.
authors.forename: Eddie
authors.initials: E
authors.lastname: Weitzberg
mesh_terms: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D003545:Cysteine / Q000031:analogs & derivatives / Q000096:biosynthesis; D016503:Drug Delivery Systems / Q000379:methods*; D008826:Microbial Sensitivity Tests; D009589:Nitrogen Oxides / Q000494:pharmacology*; D026403:S-Nitrosothiols; D012977:Sodium Nitrite / Q000737:chemistry; D001743:Urinary Bladder / Q000382:microbiology; D014546:Urinary Catheterization / Q000295:instrumentation; D062885:Urinary Catheters / Q000382:microbiology*; D014556:Urine / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D009589:Nitrogen Oxides; D026403:S-Nitrosothiols; C021315:S-nitrosocysteine; D003545:Cysteine; D012977:Sodium Nitrite
keywords: Bacteria; Free radicals; Infection; Nitric oxide; Nitrite; Urinary tract